Prognostic Factors and a Nomogram Predicting Survival in Patients with Breast Ductal Carcinoma in situ with Microinvasion: A Population-Based Study

Figures & data

Figure 1 Flowchart of the case selection process in the study.

Abbreviations: DCISM, ductal carcinoma in situ with microinvasion; ER, estrogen receptor; PR, progesterone receptor.

Table 1 The Individual Characteristics of Variables Involved in the Study

Characteristics	Training Set		Validating Set
	No. of Patients	%	No. of Patients	%
Year of diagnosis
1988–2001	391	10.3	183	11.2
2002–2015	3415	89.7	1449	88.8
Age
<40	201	5.3	71	4.4
40–50	915	24.0	402	24.6
51–70	2048	53.8	863	52.9
>70	642	16.9	296	18.1
Marital status
Married	1284	33.7	542	33.2
Not married^a	2357	61.9	1036	63.5
Unknown	165	4.3	54	3.3
Race
Caucasian	2894	76.0	1231	75.4
African American	445	11.7	188	11.5
American Indian/Alaskan native, or Asian/Pacific Islander	467	12.3	213	13.1
AJCC N stage
N0	3511	92.2	1527	93.6
N1	248	6.5	94	5.8
N2	32	0.8	7	0.4
N3	15	0.4	4	0.2
Primary site
Upper-inner quadrant of breast	375	9.9	137	8.4
Lower-inner quadrant of breast	249	6.5	122	7.5
Upper-outer quadrant of breast or axillary tail of breast	1341	35.2	616	37.7
Lower-outer quadrant of breast	268	7.0	106	6.5
Nipple or central portion of breast	217	5.7	106	6.5
Overlapping lesion of breast	1356	35.6	545	33.4
Laterality
Right-origin of primary	1900	49.9	800	49.0
Left-origin of primary	1906	50.1	832	51.0
Grade
I	811	21.3	344	21.1
II	1478	38.8	693	42.5
III and undifferentiated	1517	39.9	595	36.5
ER status
Positive	2685	70.5	1181	72.4
Negative	1121	29.5	451	27.6
PR
Positive	2177	57.2	971	59.5
Negative	1629	42.8	661	40.5
Surgery
No surgery	23	0.6	16	1.0
Lumpectomy	2155	56.6	940	57.6
Mastectomy	1628	42.8	676	41.4
Chemotherapy
No	3392	89.1	1499	91.9
Yes	412	10.8	133	8.1
Radiation
No	1998	52.5	827	50.7
Yes	1808	47.5	805	49.3

Note: ^aIncludes divorced, separated, single (never married), and widowed.

Abbreviations: AJCC, American Joint Committee on Cancer; ER, estrogen receptor; PR, progesterone receptor.

Figure 2 Nomogram to calculate risk score and predict 5-year, 10-year, and 15-year BCSS probability. By summing the points identified on the top scale for each independent variable and drawing a vertical line from the total points scale to the 5-year, 10-year, and 15-year BCSS, the corresponding survival probability can be obtained. Age, 1 = under 40 years, 2 = 41–50 years, 3 = 51–70 years, 4 = over 70 years; Race, 1 = Caucasian, 2 = African American, 3 = American Indian/Alaska Native or Asian/Pacific Islander; Year of diagnosis, 1 = 1988–2001, 2 = 2002–2015; AJCC 6th N stage, 0 = N0 stage, 1 = N1 stage, 2 = N2 stage, 3 = N3 stage; Surgery, 0 = no surgery, 1 = lumpectomy, 2 = mastectomy; Chemotherapy, 0 = no, 1 = yes; PR status, 0 = negative, 1 = positive.

Abbreviations: BCSS, breast cancer-specific survival; PR, progesterone receptor.BCSS, breast cancer-specific survival; PR, progesterone receptor.

Table 2 Univariate and Multivariate Analyses of Breast Cancer-Specific Mortality

Variable	Univariate Analysis	Multivariate Analysis
	HR (95% CI)	HR (95% CI)
Year of diagnosis
1988–2001	References	References
2002–2015	0.44(0.30,0.65)	0.56(0.37,0.84)
Age
<40	References	References
40–50	0.35(0.19,0.66)	0.41(0.22,0.78)
51–70	0.35(0.20,0.61)	0.53(0.30,0.96)
>70	0.75(0.41,1.31)	1.40(0.72,2.74)
Marital status
Not married^a	References	References
Married	0.67(0.47,0.96)	0.79(0.53,1.16)
Unknown	0.75(0.27,2.03)	0.57(0.20,1.60)
Race
Caucasian	References	References
African American	2.15(1.40,3.31)	1.69(1.06,2.68)
American Indian/Alaskan native, or Asian/Pacific Islander	0.72(0.38,1.39)	0.75(0.39,1.46)
AJCC N stage
N0	References	References
N1	5.14(3.42,7.74)	2.69(1.57,4.62)
N2	7.71(3.36,17.66)	4.29(1.64,11.19)
N3	18.86(7.64,46.53)	9.32(3.23,26.94)
Primary site
Upper-outer quadrant of breast or axillary tail of breast	References	References
Upper-inner quadrant of breast	1.30(0.68,2.50)	1.23(0.63,2.43)
Lower-inner quadrant of breast	0.56(0.20,1.58)	0.62(0.22,1.76)
Lower-outer quadrant of breast	0.84(0.36,1.99)	0.86(0.36,2.06)
Nipple or central portion of breast	1.26(0.59,2.70)	1.10(0.51,2.39)
Overlapping lesion of breast	1.62(1.08,2.45)	1.40(0.92,2.13)
Laterality
Left-origin of primary	References	References
Right-origin of primary	0.86(0.60,1.22)	0.75(0.52,1.07)
Grade
I	References	References
II	1.30(0.74,2.27)	1.14(0.64,2.03)
III and undifferentiated	1.77(1.04,3.02)	1.23(0.69,2.20)
ER status
Negative	References	References
Positive	0.74(0.52,1.06)	1.49(0.92,2.42)
PR
Negative	References	References
Positive	0.58(0.41,0.83)	0.50(0.32,0.80)
Surgery
No surgery	References	References
Lumpectomy	0.06(0.03,0.13)	0.11(0.04,0.28)
Mastectomy	0.11(0.05,0.23)	0.12(0.05,0.28)
Chemotherapy
No	References	References
Yes	4.47(3.10,6.44)	2.21(1.29,3.76)
Radiation
No	References	References
Yes	0.66(0.46,0.94)	0.83(0.51,1.36)

Note: ^aIncludes divorced, separated, single (never married), and widowed.

Abbreviations: HR, hazard ratio; CI, confidence interval; ER, estrogen receptor; PR, progesterone receptor.

Figure 3 ROC curves and calibration plots for predicting BCSS. ROC curves of the nomogram predicting prognosis in the training set (A) and the validating set (B). Calibration curves comparing predicted and actual BCSS proportions at 5-year (C), 10-year (D), and 15-years (E), separately. Each point in the plot refers to a group of patients, with the nomogram predicted probability of survival shown on x axis and actual survival proportion shown on y axis. Distributions of predicted survival probabilities are plotted at the top. Error bars represent 95% confidence intervals. (F) 5-year, 10-year and 15-year BCSS in patients with each subtype of breast ductal carcinoma in situ with microinvasion.

Abbreviations: AUC, area under the ROC curve; BCSS, breast cancer-specific survival; ER, estrogen receptor; PR, progesterone receptor; ROC, receiver operating characteristic curve.

Figure 4 The survival curves for DCISM patients with and without chemotherapy and radiotherapy after 1:1 matching. (A) Kaplan-Meier curve depicting the association between chemotherapy and breast DCISM. Kaplan-Meier curve depicting the association between chemotherapy and breast DCISM in ER+PR+ (B), ER+PR-/ER-PR+ (C) and ER-PR- subgroup (D). (E) Kaplan-Meier curve depicting the association between radiotherapy and breast DCISM.

Abbreviations: DCISM, ductal carcinoma in situ with microinvasion; ER, estrogen receptor; PR, progesterone receptor.

Table 3 BCSS of Patients with DCISM Between Statistically Matched Chemotherapy and Non-Chemotherapy Groups

Variable	Group	Chemotherapy	Non-Chemotherapy
5-year BCSS	All	95.1%	81.1%
	ER+PR+	97.6%	97.6%
	ER+PR-/ER-PR+	97.8%	80.1%
	ER-PR-	95.1%	81.1%
10-year BCSS	All	89.7%	81.1%
	ER+PR+	91.9%	93.9%
	ER+PR-/ER-PR+	97.8%	93.9%
	ER-PR-	89.7%	81.1%
15-year BCSS	All	89.7%	81.1%
	ER+PR+	90.0%	93.9%
	ER+PR-/ER-PR+	97.8%	73.4%
	ER-PR-	89.7%	81.1%

Abbreviations: BCSS, breast cancer-specific survival; ER, estrogen receptor; PR, progesterone receptor.